Xofluza, which has not yet been assessed by NICE for routine NHS prescribing, is indicated for the treatment of uncomplicated influenza and the post-exposure prophylaxis of influenza in individuals aged 12 years and above.
A single dose of two Xofluza tablets is taken as soon as possible within 48 hours of symptom onset or suspected exposure.
As a prodrug, baloxavir marboxil is converted in the body to baloxavir, the active form. Baloxavir acts on the cap-dependent endonuclease of the influenza virus to inhibit viral transcription and replication.
In otherwise healthy outpatients with acute uncomplicated influenza enrolled in the randomised, double-blind CAPSTONE-1 phase III study, baloxavir was superior to placebo in alleviating influenza symptoms, and superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of treatment. The intention-to-treat infected population comprised 1064 patients aged 12–64 years; 84.8% to 88.1% of patients in each of the three treatment groups had influenza A (H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% CI 49.5–58.5) with baloxavir versus 80.2 hours (95% CI 72.6–87.1) with placebo (p<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir.
Baloxavir also has superior efficacy to placebo and similar efficacy to oseltamivir for ameliorating influenza symptoms in outpatients at high risk of developing influenza-associated complications, as shown by the randomised, double-blind CAPSTONE-2 phase III study. The modified intention-to-treat population comprised 1163 patients aged ≥12 years, of whom the majority had influenza A H3N2 (48%) or influenza B (42%). The median time to improvement of influenza symptoms in the baloxavir group (73.2 hours [95% CI 67.2–85.1]) was shorter than that in the placebo group (102.3 hours [92.7–113.1]; p<0.0001) and similar to the time in the oseltamivir group (81.0 hours [95% CI 69.4–91.5]).
Combining baloxavir with neuraminidase inhibitors did not result in superior clinical outcomes compared with neuraminidase inhibitors alone in hospitalised patients with severe influenza enrolled in the randomised, double-blind FLAGSTONE phase III study.
Baloxavir has demonstrated efficacy in post-exposure prophylaxis of influenza. In a double-blind phase III trial conducted during the 2018–19 flu season in Japan, 752 household contacts of 545 index patients were randomised to receive baloxavir or placebo. Of the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. In the modified intention-to-treat population (n=749), the percentage of patients who developed clinical influenza was significantly lower in the baloxavir group than in the placebo group (1.9% vs 13.6%) (adjusted risk ratio 0.14 [95% CI 0.06–0.30]; p<0.001). Baloxavir was effective in high-risk, paediatric, and unvaccinated patients.
Hypersensitivity reactions to baloxavir marboxil, including reports of anaphylaxis and less severe forms of hypersensitivity reactions such as urticaria and angioedema, have been observed in the postmarketing setting. Of these, only urticaria has been observed in clinical studies, at an estimated frequency of 'uncommon'.